title: T helper cells promote disease progression of osteoarthritis by inducing macrophage inflammatory protein-1γ.
abstract: OBJECTIVE
  Immune cells are involved in the pathogenesis of osteoarthritis (OA). We examined the effects of T helper (Th) cells, which induce the expression of macrophage inflammatory protein (MIP-1γ), on the progression of OA.
  
  
  METHODS
  Using anterior cruciate ligament-transection (ACLT), we induced OA in one hind-leg knee joint of B6 mice. The CD4(+) T cells from splenocytes and synovium were flow-cytometrically and immunochemically evaluated, respectively. The knee joints were histologically assessed for manifestations of OA. MIP-1γ levels and nuclear factor-κB (NF-κB) in the knee joints were measured using enzyme-linked immunosorbent and immunoblotting assays, respectively; osteoclastogenesis was detected by tartrate-resistant acid phosphatase (TRAP) staining. The inflammatory responses and MIP-1γ expression were examined using immunohistochemistry.
  
  
  RESULTS
  The number of CD4(+) T cells and the expression of interferon-γ (IFN-γ) increased during OA onset (30 days after ACLT) and then decreased at a later stage of OA (90 days after ACLT). Tissue damage induced by CD4(+) T cells was evident at the later stage. The activation of CD4(+) T cells induced the expression of MIP-1γ and NF-κB. The expression of MIP-1γ can be detected in synovium which CD4(+) T cells were infiltrated. The increased MIP-1γ expression caused an increase in the number of osteoclasts in joints. The regulation of CD4(+) T cells was accompanied by increased macrophage infiltration and matrix metalloproteinase (MMP)-9 expression. Histopathological examinations revealed that CD4(+) T cell knockout (CD4(-/-)) mice had less expression of MIP-1γ and slower cartilage degeneration than control mice had.
  
  
  CONCLUSIONS
  CD4(+) T cells were activated during the onset of OA, but cartilage damage was more prominent at a later stage. CD4(+) T cells were involved in the pathogenesis of OA: they induced MIP-1γ expression and subsequent osteoclast formation.
authors.affiliation: Orthopedics Department, Tainan Hospital, Department of Health, Executive Yuan, Taiwan.
authors.forename: P-C
authors.initials: PC
authors.lastname: Shen
authors.forename: C-L
authors.initials: CL
authors.lastname: Wu
authors.forename: I-M
authors.initials: IM
authors.lastname: Jou
authors.forename: C-H
authors.initials: CH
authors.lastname: Lee
authors.forename: H-Y
authors.initials: HY
authors.lastname: Juan
authors.forename: P-J
authors.initials: PJ
authors.lastname: Lee
authors.forename: S-H
authors.initials: SH
authors.lastname: Chen
authors.forename: J-L
authors.initials: JL
authors.lastname: Hsieh
mesh_terms: D000818:Animals; D018450:Disease Progression; D005434:Flow Cytometry; D007150:Immunohistochemistry; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D020370:Osteoarthritis, Knee / Q000276:immunology* / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*
chemical_list: D019402:Macrophage Inflammatory Proteins; D016328:NF-kappa B